公开(公告)号：US6080779A

公开(公告)日：2000-06-27

申请号：US96957

申请日：1998-06-12

申请人： Shirley R. Gasper ,  Robert R. West ,  Theresa Martinez ,  Kirk G. Robbins ,  Patricia A. McKernan ,  Nand Baindur ,  Virender M. Labroo ,  Gregory R. Mundy

发明人： Shirley R. Gasper ,  Robert R. West ,  Theresa Martinez ,  Kirk G. Robbins ,  Patricia A. McKernan ,  Nand Baindur ,  Virender M. Labroo ,  Gregory R. Mundy

IPC分类号： A61K31/22 ,  A61K31/366 ,  A61K31/404 ,  A61K31/335 ,  A61K31/33 ,  A61K31/66

CPC分类号： A61K31/404 ,  A61K31/22 ,  A61K31/366

摘要： Compounds of the formula ##STR1## wherein X in each of formulas (1) and (2) represents a substituted or unsubstituted alkylene, alkenylene, or alkynylene linker of 2-6 C;Y represents one or more carbocyclic or heterocyclic rings; when two or more rings are present in Y, they may optionally be fused; andR' represents a cation, H or a substituted or unsubstituted alkyl group of 1-6 C; andthe dotted lines represent optional .pi.-bonds,promote bone formation and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation. These compounds can be used in combination with other bone growth-promoting compounds and/or estrogens and/or bisphosphonates for this purpose.

摘要翻译： 式（1）和（2）各自表示X为2-6的取代或未取代的亚烷基，亚烯基或亚炔基连接基的式 Y表示一个或多个碳环或杂环; 当Y中存在两个或更多个环时，它们可以任选地稠合; R'表示1-6个C的阳离子，H或取代或未取代的烷基; 虚线表示可选的pi-键，促进骨形成，因此可用于治疗骨质疏松症，骨折或缺陷，原发性或继发性甲状旁腺功能亢进，牙周病或缺陷，转移性骨病，溶骨性骨病，整形外手术 假体关节手术和牙植入后。 为了此目的，这些化合物可以与其它骨生长促进化合物和/或雌激素和/或二膦酸盐组合使用。

公开(公告)号：US5994358A

公开(公告)日：1999-11-30

申请号：US808744

申请日：1997-02-28

申请人： Charles Petrie ,  Mark W. Orme ,  Nand Baindur ,  Kirk G. Robbins ,  Maria Kontoyianni ,  Gregory R. Mundy

发明人： Charles Petrie ,  Mark W. Orme ,  Nand Baindur ,  Kirk G. Robbins ,  Maria Kontoyianni ,  Gregory R. Mundy

IPC分类号： A61K31/47 ,  A61K31/498 ,  A61K31/655 ,  A61K31/495 ,  A61K31/35 ,  A61K31/38

CPC分类号： A61K31/655 ,  A61K31/47 ,  A61K31/498

摘要： Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

公开(公告)号：US20130122053A1

公开(公告)日：2013-05-16

申请号：US13625527

申请日：2012-09-24

申请人： Trustees of Dartmouth College ,  Osteoscreen, Inc. ,  The Regents of the University of California ,  Rutgers, The State University of new Jersey

发明人： Michael B. SPORN ,  Karen T. Liby ,  Tadashi Honda ,  Gregory Mundy ,  Ross Garrett ,  Hari Reddi ,  Gordon W. Gribble ,  Takahiro Niikura ,  Nanjoo Suh

IPC分类号： A61K31/4164 ,  A61K38/18 ,  A61K35/32 ,  A61K31/277 ,  A61K9/00

CPC分类号： A61K31/4164 ,  A61K9/00 ,  A61K31/26 ,  A61K31/277 ,  A61K35/32 ,  A61K38/1841 ,  C12N5/0655 ,  C12N2501/999 ,  Y02A50/395 ,  A61K2300/00

摘要： The present invention concerns methods for stimulating the growth and repair of bone and cartilage using synthetic triterpenoids and tricyclic-bis-enones. Examples of suitable triterpenoids include CDDO, CDDO-Me, CDDO-Im, and CDDO-Ethylamide. Examples of tricyclic-bis-enones include TBE-31 and TBE-34.

摘要翻译： 本发明涉及使用合成三萜类化合物和三环双酮来刺激骨和软骨的生长和修复的方法。 合适的三萜类化合物的实例包括CDDO，CDDO-Me，CDDO-Im和CDDO-乙酰胺。 三环双酮的实例包括TBE-31和TBE-34。

公开(公告)号：US5990169A

公开(公告)日：1999-11-23

申请号：US806771

申请日：1997-02-26

申请人： Charles Petrie ,  Mark W. Orme ,  Nand Baindur ,  Kirk G. Robbins ,  Scott M. Harris ,  Gregory R. Mundy

发明人： Charles Petrie ,  Mark W. Orme ,  Nand Baindur ,  Kirk G. Robbins ,  Scott M. Harris ,  Gregory R. Mundy

IPC分类号： A61K31/196 ,  A61K31/445 ,  A61K31/16 ,  A61K31/18

CPC分类号： A61K31/196

摘要： Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

公开(公告)号：US5965573A

公开(公告)日：1999-10-12

申请号：US812141

申请日：1997-03-06

申请人： Charles Petrie ,  Mark W. Orme ,  Nand Baindur ,  Kirk G. Robbins ,  Maria Kontoyianni ,  Gregory R. Mundy

发明人： Charles Petrie ,  Mark W. Orme ,  Nand Baindur ,  Kirk G. Robbins ,  Maria Kontoyianni ,  Gregory R. Mundy

IPC分类号： A61K31/196 ,  A61K31/428 ,  A61K31/444 ,  A61K31/655 ,  A61K31/33 ,  A61K31/40 ,  A61K31/445 ,  A61K31/495

CPC分类号： A61K31/444 ,  A61K31/196 ,  A61K31/428 ,  A61K31/655

摘要： Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

公开(公告)号：US08299046B2

公开(公告)日：2012-10-30

申请号：US11941723

申请日：2007-11-16

申请人： Michael B. Sporn ,  Karen T. Liby ,  Tadashi Honda ,  Gregory Mundy ,  Ross Garrett ,  Hari Reddi ,  Gordon W. Gribble ,  Takahiro Niikura

发明人： Michael B. Sporn ,  Karen T. Liby ,  Tadashi Honda ,  Gregory Mundy ,  Ross Garrett ,  Hari Reddi ,  Gordon W. Gribble ,  Takahiro Niikura

IPC分类号： C07D233/02

CPC分类号： A61K31/4164 ,  A61K9/00 ,  A61K31/26 ,  A61K31/277 ,  A61K35/32 ,  A61K38/1841 ,  C12N5/0655 ,  C12N2501/999 ,  Y02A50/395 ,  A61K2300/00

摘要： The present invention concerns methods for stimulating the growth and repair of bone and cartilage using synthetic triterpenoids and tricyclic-bis-enones. Examples of suitable triterpenoids include CDDO, CDDO-Me, CDDO-Im, and CDDO-Ethylamide. Examples of tricyclic-bis-enones include TBE-31 and TBE-34.

摘要翻译： 本发明涉及使用合成三萜类化合物和三环双酮刺激骨和软骨的生长和修复的方法。 合适的三萜类化合物的实例包括CDDO，CDDO-Me，CDDO-Im和CDDO-乙酰胺。 三环双酮的实例包括TBE-31和TBE-34。

公开(公告)号：US20080233195A1

公开(公告)日：2008-09-25

申请号：US11941723

申请日：2007-11-16

申请人： Michael B. Spoorn ,  Karen T. Liby ,  Tadashi Honda ,  Gordon Gribble ,  Gregory Mundy ,  Ross Garrett ,  Hari Reddi ,  Takahiro Niikura

发明人： Michael B. Spoorn ,  Karen T. Liby ,  Tadashi Honda ,  Gordon Gribble ,  Gregory Mundy ,  Ross Garrett ,  Hari Reddi ,  Takahiro Niikura

IPC分类号： A61K9/00 ,  C12N5/00 ,  A61K31/122 ,  A61P19/00 ,  A61K35/12

CPC分类号： A61K31/4164 ,  A61K9/00 ,  A61K31/26 ,  A61K31/277 ,  A61K35/32 ,  A61K38/1841 ,  C12N5/0655 ,  C12N2501/999 ,  Y02A50/395 ,  A61K2300/00

摘要： The present invention concerns methods for stimulating the growth and repair of bone and cartilage using synthetic triterpenoids and tricyclic-bis-enones. Examples of suitable triterpenoids include CDDO, CDDO-Me, CDDO-Im, and CDDO-Ethylamide. Examples of tricyclic-bis-enones include TBE-31 and TBE-34.

摘要翻译： 本发明涉及使用合成三萜类化合物和三环双酮来刺激骨和软骨的生长和修复的方法。 合适的三萜类化合物的实例包括CDDO，CDDO-Me，CDDO-Im和CDDO-乙酰胺。 三环双酮的实例包括TBE-31和TBE-34。

公开(公告)号：US06838436B1

公开(公告)日：2005-01-04

申请号：US09695807

申请日：2000-10-23

申请人： Gregory R. Mundy ,  I. Ross Garrett ,  Jorge Gianny Rossini

发明人： Gregory R. Mundy ,  I. Ross Garrett ,  Jorge Gianny Rossini

IPC分类号： A61K8/64 ,  A61K31/00 ,  A61K31/351 ,  A61K31/365 ,  A61K31/4015 ,  A61K31/522 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61K45/06 ,  A61Q7/00 ,  A61K38/00

CPC分类号： A61K8/64 ,  A61K31/00 ,  A61K31/351 ,  A61K31/365 ,  A61K31/4015 ,  A61K31/522 ,  A61K31/7042 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61K45/06 ,  A61Q7/00 ,  A61K2300/00

摘要： The present invention relates to compounds that inhibit the activity of the proteasome or the productions of proteasomal proteins and promote bone formation and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgey, and post-dental implantation, in subject where this is desirable.

摘要翻译： 本发明涉及抑制蛋白酶体活性或蛋白酶体蛋白的产生并促进骨形成的化合物，因此可用于治疗骨质疏松症，骨折或缺陷，原发性或继发性甲状旁腺功能亢进，牙周病或缺陷，转移性骨病， 溶骨性骨病，整形后手术，假体后关节活动和牙周后植入术，这是可取的。

公开(公告)号：US6022887A

公开(公告)日：2000-02-08

申请号：US989862

申请日：1997-12-12

申请人： Shirley R. Gasper ,  Robert R. West ,  Theresa Martinez ,  Kirk G. Robbins ,  Patricia A. McKernan ,  Nand Baindur ,  Virender M. Labroo

发明人： Shirley R. Gasper ,  Robert R. West ,  Theresa Martinez ,  Kirk G. Robbins ,  Patricia A. McKernan ,  Nand Baindur ,  Virender M. Labroo

IPC分类号： A61K31/216 ,  A61K31/22 ,  A61K31/366 ,  A61K31/381 ,  A61K31/404 ,  A61K31/405 ,  A61P19/08 ,  A61P19/10 ,  A01N43/16 ,  C07D309/00

CPC分类号： A61K31/405 ,  A61K31/22 ,  A61K31/366 ,  A61K31/404

摘要： Compounds of the formula ##STR1## wherein X in each of formulas (1) and (2) represents a substituted or unsubstituted alkylene, alkenylene, or alkynylene linker of 2-6C;Y represents one or more carbocyclic or heterocyclic rings; when two or more rings are present in Y, they may optionally be fused; andR' represents a cation, H or a substituted or unsubstituted alkyl group of 1-6C; andthe dotted lines represent optional .pi.-bonds,promote bone formation and are thus usefull in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation.

摘要翻译： 式（1）和（2）中的X表示取代或未取代的2-6C的亚烷基，亚烯基或亚炔基接头; Y表示一个或多个碳环或杂环; 当Y中存在两个或更多个环时，它们可以任选地稠合; 和R'表示1-6个C的阳离子，H或取代或未取代的烷基; 并且虚线代表可选的pi-键，促进骨形成，因此可用于治疗骨质疏松症，骨折或缺陷，原发性或继发性甲状旁腺功能亢进，牙周病或缺陷，转移性骨病，溶骨性骨病，整形后手术 假体关节手术和牙植入后。

公开(公告)号：US6017940A

公开(公告)日：2000-01-25

申请号：US806770

申请日：1997-02-26

申请人： Charles Petrie ,  Mark W. Orme ,  Nand Baindur ,  Kirk G. Robbins ,  Gregory R. Mundy

发明人： Charles Petrie ,  Mark W. Orme ,  Nand Baindur ,  Kirk G. Robbins ,  Gregory R. Mundy

IPC分类号： A61K31/196 ,  A61K31/4184 ,  A61K31/428 ,  A61K31/444 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/498 ,  A61K31/517 ,  A61K31/53 ,  A61K31/655 ,  A61K31/425

CPC分类号： A61K31/655 ,  A61K31/196 ,  A61K31/4184 ,  A61K31/428 ,  A61K31/444 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/498 ,  A61K31/517 ,  A61K31/53

摘要： Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.